» Articles » PMID: 19958503

Computational Identification and Experimental Validation of PPRE Motifs in NHE1 and MnSOD Genes of Human

Overview
Journal BMC Genomics
Publisher Biomed Central
Specialty Genetics
Date 2009 Dec 5
PMID 19958503
Citations 22
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Activation of PPARs has been reported to inhibit the proliferation of malignant cells from different lineages. They are involved in transcription regulation of genes upon activation by a ligand. The binding of PPARs to the promoter sequence either represses or activates the gene. Hence, PPARs represent promising targets for cancer treatment because of their anti-proliferative and pro-apoptotic activities. Here we computationally identified PPAR binding regions in NHE1 and MnSOD. We further validated the predictions in vitro.

Results: Our results computationally predicted the presence of 2 PPRE motifs in NHE1 and 3 PPRE motifs in MnSOD. We experimentally confirmed the true motifs and their regulation by PPAR.

Conclusion: Our results suggest that both NHE1 and MnSOD have PPRE binding motif in their upstream/promoter region and hence are regulated by PPAR upon ligand binding.

Citing Articles

Bmp8a deletion leads to obesity through regulation of lipid metabolism and adipocyte differentiation.

Zhong S, Chen L, Li X, Wang X, Ji G, Sun C Commun Biol. 2023; 6(1):824.

PMID: 37553521 PMC: 10409762. DOI: 10.1038/s42003-023-05194-2.


Hepatic transcriptome analysis identifies genes, polymorphisms and pathways involved in the fatty acids metabolism in sheep.

Gunawan A, Listyarini K, Harahap R, Jakaria , Roosita K, Sumantri C PLoS One. 2021; 16(12):e0260514.

PMID: 34941886 PMC: 8699643. DOI: 10.1371/journal.pone.0260514.


Epigenetic derepression converts PPARγ into a druggable target in triple-negative and endocrine-resistant breast cancers.

Loo S, Syn N, Koh A, Teng J, Deivasigamani A, Tan T Cell Death Discov. 2021; 7(1):265.

PMID: 34580286 PMC: 8476547. DOI: 10.1038/s41420-021-00635-5.


NRF2 and PPAR-γ Pathways in Oligodendrocyte Progenitors: Focus on ROS Protection, Mitochondrial Biogenesis and Promotion of Cell Differentiation.

De Nuccio C, Bernardo A, Troiano C, Brignone M, Falchi M, Greco A Int J Mol Sci. 2020; 21(19).

PMID: 33003644 PMC: 7583077. DOI: 10.3390/ijms21197216.


PPARδ is a regulator of autophagy by its phosphorylation.

Gou Q, Jiang Y, Zhang R, Xu Y, Xu H, Zhang W Oncogene. 2020; 39(25):4844-4853.

PMID: 32439863 DOI: 10.1038/s41388-020-1329-x.


References
1.
Kumar A, Piedrafita F, Reynolds W . Peroxisome proliferator-activated receptor gamma ligands regulate myeloperoxidase expression in macrophages by an estrogen-dependent mechanism involving the -463GA promoter polymorphism. J Biol Chem. 2003; 279(9):8300-15. DOI: 10.1074/jbc.M311625200. View

2.
Mukhopadhyay S, Das S, Mukherjee S . Expression of Mn-Superoxide Dismutase Gene in Nontumorigenic and Tumorigenic Human Mammary Epithelial Cells. J Biomed Biotechnol. 2004; 2004(4):195-202. PMC: 555772. DOI: 10.1155/S1110724304401016. View

3.
Lapillonne H, Konopleva M, Tsao T, Gold D, McQueen T, Sutherland R . Activation of peroxisome proliferator-activated receptor gamma by a novel synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces growth arrest and apoptosis in breast cancer cells. Cancer Res. 2003; 63(18):5926-39. View

4.
Desvergne B, Wahli W . Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev. 1999; 20(5):649-88. DOI: 10.1210/edrv.20.5.0380. View

5.
Issemann I, Green S . Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature. 1990; 347(6294):645-50. DOI: 10.1038/347645a0. View